Protected amino acids, that is, amino acids having the amine functional group thereof blocked by an amino-protective group, are sometimes called N-blocked amino acids. These protected amino acids are widely used in the field of biochemistry. Commercially, amino-protected amino acids are useful as starting materials for the synthesis of polypeptides and proteins. These synthetic polypeptides and proteins have important application in the fields of medicine, industry, pharmacology and most especially immunology.
L-aspartic acid derivatives are particularly useful in the synthesis of biologically-active polypeptides as disclosed in U.S. Pat. No. 4,298,523 to Heavner, pertinent portions of which are incorporated herein by reference.
Peptide syntheses are hampered by low yields of relatively pure product when synthesis is attempted without first preventing undesired reactions of the amine portion of the molecule. Undesired reactions are prevented by attaching a protective group to the amine portion of the molecule, wherein the amino-protective group is unreactive in the subject reaction, but where the amino-protective group is later readily removable from the protected amino acid without causing destruction of the desired synthesis product. Tertiary butyloxycarbonyl (BOC) is a well-known protective group, and the use of BOC-protected amino acids is widely known in the art.
A frequently encountered difficulty in peptide synthesis, particularly of long chain polypeptide synthesis, is in obtaining the long chain polypeptides in relatively high yields. It is well known that unless each of the reactions in the step-wise long chain polypeptide synthesis can be made nearly quantitative, the yield of product that can be prepared from starting materials in economic amounts will be exceedingly small. The use of amino-protective groups, on the other hand, prevents the undesirable side reactions that reduce the yield of a desired polypeptide in step-wise peptide synthesis.
It is further desirable, particularly in the syntheses of biologically active peptides, that the amino-protected amino acid used be in a relatively pure, more preferably crystalline form. The relatively pure, amino-protected amino acid, as a solution or crystalline, prevents undesirable contamination of the peptide synthesis reaction with reaction products of the amino-protected amino acid, and thus allows peptide synthesis to proceed using a reasonable amount of the amino-protected amino acid in the reaction.
Crystalline tert-butyloxycarbonyl-beta-benzyl-L-aspartic acid is commercially available, for example, from Bachem Biochemicals, Torrance, Calif., Peninsula Laboratories, Inc., Belmont, Calif., as well as from other sources. The compound is relatively expensive, however.
Thus, there is a need for relatively high purity amino-protected beta-benzyl-L-aspartic acid that is relatively easy to obtain in relatively high yields and readily usable in the synthesis of biologically important compounds.